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Accurate annotation of human protein-coding small open reading frames

Functional protein-coding small open reading frames (smORFs) are emerging as an important class of genes. However, the number of translated smORFs in the human genome is unclear because proteogenomic methods are not sensitive enough, and, as we show, Ribo-Seq strategies require additional measures t...

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Detalles Bibliográficos
Autores principales: Martinez, Thomas F., Chu, Qian, Donaldson, Cynthia, Tan, Dan, Shokhirev, Maxim N., Saghatelian, Alan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7085969/
https://www.ncbi.nlm.nih.gov/pubmed/31819274
http://dx.doi.org/10.1038/s41589-019-0425-0
Descripción
Sumario:Functional protein-coding small open reading frames (smORFs) are emerging as an important class of genes. However, the number of translated smORFs in the human genome is unclear because proteogenomic methods are not sensitive enough, and, as we show, Ribo-Seq strategies require additional measures to ensure comprehensive and accurate smORF annotation. Here, we integrate de novo transcriptome assembly and Ribo-Seq into an improved workflow that overcomes obstacles with previous methods to more confidently annotate thousands of smORFs. Evolutionary conservation analyses suggest that hundreds of smORF-encoded microproteins are likely functional. Additionally, many smORFs are regulated during fundamental biological processes, such as cell stress. Peptides derived from smORFs are also detectable on human leukocyte antigen complexes, revealing smORFs as a source of antigens. Thus, by including additional validation into our smORF annotation workflow, we accurately identify thousands of unannotated translated smORFs that will provide a rich pool of unexplored, functional human genes.